chr22-41178661-G-C

Position:

• chr22-41178661-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001429.4(EP300):​c.6950G>C​(p.Arg2317Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R2317Q) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: EP300 NM_001429.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.95

Genes affected

EP300 (HGNC:3373): (E1A binding protein p300) This gene encodes the adenovirus E1A-associated cellular p300 transcriptional co-activator protein. It functions as histone acetyltransferase that regulates transcription via chromatin remodeling and is important in the processes of cell proliferation and differentiation. It mediates cAMP-gene regulation by binding specifically to phosphorylated CREB protein. This gene has also been identified as a co-activator of HIF1A (hypoxia-inducible factor 1 alpha), and thus plays a role in the stimulation of hypoxia-induced genes such as VEGF. Defects in this gene are a cause of Rubinstein-Taybi syndrome and may also play a role in epithelial cancer. [provided by RefSeq, Jul 2008]

(HGNC:):

EP300-AS1 (HGNC:50504): (EP300 antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EP300	NM_001429.4	c.6950G>C	p.Arg2317Pro	missense_variant	31/31	ENST00000263253.9
EP300	NM_001362843.2	c.6872G>C	p.Arg2291Pro	missense_variant	30/30

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EP300	ENST00000263253.9	c.6950G>C	p.Arg2317Pro	missense_variant	31/31	1	NM_001429.4	P2
	ENST00000415054.1	n.82+4402C>G		intron_variant, non_coding_transcript_variant		3
EP300-AS1	ENST00000420537.1	n.224-3837C>G		intron_variant, non_coding_transcript_variant		3
EP300	ENST00000674155.1	c.6872G>C	p.Arg2291Pro	missense_variant	30/30			A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.79
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.070
CADD	Uncertain	25
DANN	Benign	0.96
DEOGEN2	Pathogenic	0.86	D
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.049	D
MetaRNN	Uncertain	0.47	T
MetaSVM	Uncertain	-0.11	T
MutationAssessor	Benign	1.4	L
MutationTaster	Benign	0.99	D
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-4.2	D
REVEL	Uncertain	0.51
Sift	Benign	0.095	T
Sift4G	Uncertain	0.0090	D
Polyphen		0.80	P
Vest4		0.58
MutPred		0.31		Gain of glycosylation at R2317 (P = 0.0011);
MVP		0.81
ClinPred		0.96	D
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.51
gMVP		0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-41574665;